These findings mark the first time any Alzheimer’s genes have been picked from the proverbial haystack in genomic studies.

This past September, a pair of research teams announced that they had identified three new genes associated with Alzheimer’s disease. The scientists also tagged another 12 gene variants as promising candidates for further study. Previously, only four genes were known to be linked to Alzheimer’s, which affects an estimated 5 million Americans. Both reports appeared in Nature Genetics.

To pinpoint the new genes, the two groups conducted studies looking for differences between the DNA of people who have Alz­heimer’s disease and those who do not. Epidemiologist Philippe Amouyel of the Pasteur Institute of Lille in France and his colleagues closed in on genes called CR1 and CLU. The precise function of these genes is unknown, but previous research suggests they may be involved in removing a protein fragment called beta-amyloid from the brain. In people with Alzheimer’s, beta-amyloid molecules clump together and form destructive plaques.

The other team, led by medical psychologist Julie Williams of Cardiff University in Wales, noted the same CLU gene and identified another Alzheimer’s-related gene, PICALM. This gene is thought to help maintain the health of synapses, the connection points between neurons, and it, too, may regulate beta-amyloid levels in the brain.

These findings mark “the first time any novel Alzheimer’s gene has been identified in genomewide studies,” says Washington University geneticist Alison Goate, one of Williams’s coauthors. Previous studies had examined small numbers of people to confirm already-known genetic risk factors. Locating new Alzheimer’s genes will aid efforts to understand the chemical pathways that drive the disease, Amouyel says, and might eventually point the way to effective drugs to keep it at bay.